In vivo studies of the interactions between the host mucosae and commensal or pathogenic microorganisms have been profoundly influenced by the development of genetically defined and genetically engineered (transgenic and targeted mutant, or "knockout" and "knockin") mice. These animals provide powerful models for examining the role of specific genetic manipulations in complex biological systems and have generated new approaches for the study of human disease. A number of these mouse models have been critical to recent advances in our understanding of the interplay of the intestinal flora, intestinal epithelium and innate or adaptive immune cell populations in maintenance of homeostasis in the intestinal tissues - or the breakdown of these interactions in intestinal pathology [C.O. Elson, Y. Cong, N. Iqbal, and C.T, Weaver, in inflammatory Bowel Diseases: From Bench to Bedside (S.R. Targan, F. Shanahan, and LC. Karp, eds.), Dordrecht: Kluwer Academic Publishers, 2001]. The development and study of these models is resource intensive and requires special expertise that often exceeds the means of individual laboratories. The purpose of the Gnotobiotic and Genetically-Engineered Mouse Core (Core 3) will be to generate and provide gnotobiotic and genetically engineered mice to Base Grant research projects and to provide marker-assisted genotyping and pathological evaluation support services for studies using these mice. The consolidation of these resources into a single, shared core facility with expedite animal model development, facilitate technology exchange, reduce investigator costs, and provide an important resource for the recruitment of new investigators to studies of intestinal biology.